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ABCG2 Inhibitor YHO-13351 Sensitizes Cancer Stem/Initiating-like Side Population Cells to Irinotecan.


Anticancer Res. 2013 Apr;33(4):1379-86


Authors: Shishido Y, Ueno S, Yamazaki R, Nagaoka M, Matsuzaki T


Abstract

UNLABELLED: Background/Aim: The aim of this study was to determine the efficacy of the combination of irinotecan and newly-synthesized ABCG2 (breast cancer-resistant protein) inhibitor YHO-13351 in cancer chemotherapy.

MATERIALS AND METHODS: Side population (SP) and non-SP cells from the human cervical carcinoma cell line HeLa were isolated by fluorescence-activated cell sorting. The antitumor activity of combination therapy with irinotecan and YHO-13351 was evaluated in xenograft studies in athymic BALB/c nude mice.

RESULTS: While SP cells exhibited cancer stem/initiating cell-like properties and low sensitivity to irinotecan-alone, YHO-13351 sensitized them to irinotecan in both in vitro and in vivo studies. YHO-13351 in conjunction with irinotecan reduced the increase of the SP cell ratio in the tumors compared to those observed with treatment with irinotecan-alone.

CONCLUSION: Combination therapy with irinotecan and YHO-13351 would not only accelerate the antitumor effect of this regimen, but also play a crucial role in preventing resistance or relapse.

PMID: 23564776 [PubMed - in process]